The discovery of microRNAs (miRNAs) has led to a paradigm shift in our basic understanding of gene regulation. Competing endogenous RNAs (ceRNAs) are the recent entrants adding to the complexities of miRNA mediated gene regulation. ceRNAs are RNAs that share miRNA recognition elements (MREs) thereby regulating each other. It is apparent that miRNAs act as rheostats that fine-tune gene expression and maintain the functional balance of various gene networks. Thus MREs in coding and non-coding transcripts have evolved to become the crosstalk hubs of gene interactions, affecting the expression levels and activities of different ceRNAs. Decoding the crosstalk between MREs mediated by ceRNAs is critical to delineate the intricacies in gene regulation, and we have just begun to unravel this complexity.

N-acetylcysteine (NAC), a precursor of cysteine and, thereby, glutathione (GSH), acts as an antioxidant through a variety of mechanisms, including oxidant scavenging, GSH replenishment, antioxidant signaling, etc. Owing to the variety of proposed targets, NAC has a long history of use as a prescription product and in wide-ranging applications that are off-label as an over-the-counter (OTC) product. Despite its discovery in the early 1960s and its development for various indications, systematic clinical pharmacology explorations of NAC pharmacokinetics (PK), pharmacodynamic targets, drug interactions, and dose-ranging are sorely limited. Although there are anecdotal instances of NAC benefits in a variety of diseases, a comprehensive review of the use of NAC in rare diseases does not exist. In this review, we attempt to summarize the existing literature focused on NAC explorations in rare diseases targeting mitochondrial dysfunction along with the history of NAC usage, approved indications, mechanisms of action, safety, and PK characterization. Further, we introduce the research currently underway on other structural derivatives of NAC and acknowledge the continuum of efforts through pre-clinical and clinical research to facilitate further therapeutic development of NAC or its derivatives for rare diseases.

To examine the feasibility, acceptability, and preliminary effects of Hatha yoga on oxidative stress, motor function, and non-motor symptoms among individuals with Parkinson’s disease (PD). The study has a pilot randomized controlled trial design with two arms: an immediate treatment group and a wait-list control group. The yoga-for-PD program was implemented via twice weekly 60-min group-based classes for 12 weeks. Participants were assessed at baseline, 12 weeks, and 6 months post-intervention. Outcome measures included oxidative stress, motor function, physical activity, cognitive function, sleep quality, and quality of life. Data on program acceptability and yoga adherence were collected during the intervention and at 6 months post-intervention. Participants (n = 20) had a mean age of 63 years (SD 8, range 49–75) and disease duration 4.8 years (SD 2.9, range 1–13). All participants had mild-moderate disease severity; 18 (90%) were on dopaminergic medications. Seventeen participants (85%) attended at least 75% of the classes and 4 (20%) attended all classes. Most participants (n = 17) reported they “definitely enjoyed” the intervention program. No adverse events were reported. At 12 weeks, there were no major differences in blood oxidative stress markers between the two groups. Motor function based on the Unified Parkinson’s Disease Rating Scale was better in the treatment group, but their scores on sleep and outlook in Parkinson’s Disease Quality of Life (PDQUALIF) Scale and the physical activity levels based on the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire were worse than those of the control group. In within-group comparisons, motor function, cognitive function, and catalase improved but three PDQUALIF domains (social and role function, sleep, and outlook) and physical activity level worsened by the end of the yoga intervention program compared to baseline. The response rate for the 6-month follow-up survey was 74% (n = 14) with six participants (43%) who signed up for a yoga class and four (29%) who practiced it independently. Health problems were the main barrier to yoga practice. Yoga is feasible and acceptable and may serve as a complementary method for improving motor function in PD. Further research using a larger sample size is needed to determine its impact on oxidative stress and non-motor symptoms. ClinicalTrials.gov Registration Number: NCT02509610031.